Immune cell metabolism and NK mediated immunotherapy
Lymphocytes and phagocytes, through their adaptive and innate cytotoxic functions, contribute to the pathogenesis of autoimmune diseases and mediate transplant rejection thus hampering approaches in regenerative medicine. Furthermore, if correctly activated, they can mediate strong anti-tumor responses. Our goal is to better understand the mechanisms regulating their activation and differentiation in response to self and foreign signals. This will allow us not only to set the basis for new immunotherapeutic approaches aiming to prevent pathological responses but, also, to enhance anti-tumor cytotoxic responses.
NK cell differentiation in pathological conditions:
We have initiated the challenging project of investigating human NK cell activation in cancer and bone marrow engrafted patients. We are seeking to unravel new functions of several genes and miRNA regulated upon NK cell activation and evaluate the use of drugs with metabolic effects on cytotoxic lymphocyte-based clinical protocols. Our research led us to develop an original protocol to produce in vitro NK cells for clinical/industrial use in collaboration with a private company. Now we are seeking new goals that can be summarized as follow:
Martin Villalba has 68 articles at 09/07/2016. H-index: 32.
Selected Publications from 2008:
- Garaude J et al. Sumoylation regulates the transcriptional activity of JunB in T lymphocytes. J Immunol. 180(9):5983-90 (2008). (IF: 5.36)
- Garaude J et al. Impaired anti-leukemic immune response in PKCtheta-deficient mice. Molecular Immunology, 45(12):3463-9 (2008). (IF: 3.03)
- Cherni S et al. ERK5 knockdown generates mouse leukemia cells with low MHC-I levels that activate NK cells and block tumorigenesis. J Immunol. Mar 15;182(6):3398-405 (2009). (IF: 5.36)
- Aguiló JI et al. PKCtheta is required for NK cell activation and in vivo control of tumor progression. J Immunol. 182(4):1972-81 (2009). (IF: 5.36)
- Clapé C. miR-143 Interferes with ERK5 Signaling, and Abrogates Prostate Cancer Progression in Mice. PLoS One. Oct 26;4(10):e7542 (2009).
- Charni S et al. Oxidative Phosphorylation induces de novo expression of the Major Histocompatibility Complex-I in tumor cells through de ERK5 pathway. J Immunol. Sep 15;185(6):3498-503 (2010). Jacques Neefjes and Malgorzata Garstka, The Netherlands Cancer Institute, Netherlands. F1000 Immunology. IF: (5.36)
- Kaminski S et al. The protooncogene Vav1 controls murine leukemia virus-induced T cell leukemogenesis. Oncoimmunology. 2012 Aug 1;1(5):600-608. (IF: 6.28)
- Moeez G et al. The NF-kB member p65 controls glutamine metabolism through miR23. The International Journal of Biochemistry and Cell Biology. 2012 May 24;44(9):1448-1456. (IF: 4.23)
- Martin Villalba et al. From tumor cell metabolism to tumor immune escape. The International Journal of Biochemistry and Cell Biology. 2013 Jan; 45(1):106-13. (IF: 4.23)
- Anel A et al. Protein Kinase C-q (PKCq) in Natural Killer (NK) cell function and anti-tumor immunity. Frontiers in Immunology. 2012;3:187. Epub 2012 Jul 5. (IF: 1.79)
- Villalba M et al. Chemical metabolic inhibitors for the treatment of blood-borne cancers. Anticancer Agents Med Chem. 2014 Feb;14(2):223-32. (IF: 2.92)
- Auger S. Controlled epstein-barr virus reactivation after allogenic tranplantation is associated with improved survival. European Journal of Haematology. 2014 May;92(5):421-8. IF: 2.41.
- Sanchez-Martinez D et al. All-trans retinoic acid (ATRA) induces miR-23a expression, decreases CTSC expression and granzyme B activity leading to impaired NK cell cytotoxicity. The International Journal of Biochemistry and Cell Biology. 2014 Apr;49:42-52. (IF: 4.23)
- Lopez-Royuela N et al. ERK5 modulates the antioxidant response by transcriptionally controlling Sirt1 expression in leukemic cells. The International Journal of Biochemistry and Cell Biology. 2014 May 28;53C:253-261. doi: 10.1016. (IF: 4.23)
- Ramírez-Comet N et al. IFN-α signaling through PKC-θ is essential for anti-tumoral NK cell function. Oncoimmunology. 3 (8) 2014. (IF: 6.28)
- Bouche G. Lessons from the fourth metronomic and anti-angiogenic therapy meeting, 24-25 June 2014, Milan. Ecancermedicalscience. Ecancermedicalscience. 2014 Sep 9;8:463
- Catalán E et al. MHC-I modulation due to metabolic changes regulates tumor sensitivity to CTL and NK cells. Oncoimmunology. 2015 4:1, e985924. (IF: 6.28)
- Sánchez-Martínez D et al. Human NK cells activated by EBV+ lymphoblastoid cells overcome anti-apoptotic mechanisms of drug resistance in haematological cancer cells. Oncoimmunology. 2015. (IF: 6.28)
- Allende-Vega N et al.. The presence of wild type p53 in hematological cancers improves the efficacy of combinational therapy targeting metabolism. Oncotarget 2015 Jul 30. [Epub ahead of print] PMID: 26231043. IF : 6.63.
- Krzywinska E et al.. Identification of anti tumor cells carrying natural killer (NK) cell antigens in patients with hematological cancers. EBioMedicine 2 (2015), pp. 1364-1376 (supported by Cell Press and The Lancet). Comments on : Trace Evidence: Identifying Natural Cancer Killers After the Crime. Jolie R. Schafer and Dean A. Lee. EBioMedicine. 2015 Sep 24;2(10):1276-7
- René C et al. 5’ and 3’ untranslated regions contribute to the differential expression of specific HLA-A alleles. Eur J Immunol. 2015 Dec;45(12):3454-63. IF: 4.034.
- Abrar Ul Haq Khan et al.. Human leukemic cells performing oxidative phosphorylation (OXPHOS) generate an antioxidant response independently of reactive oxygen species (ROS) generation. EBioMedicine 3 (2016), pp 43-53. Comments on: Keep Harm at bay: Oxidative Phosphorylation Induces Nrf2-Driven Antioxidant Response via ERK5/MEF2/miR-23a Signaling to Keap-1. Michael Danilenko, George P. Studzinski. EBioMedicine. 2016 Jan 11;3:4-5.
- Krzywinska E et al. CD45 isoform profile identifies NK subsets with differential activity. PLoS One. 2016 Apr 21;11(4):e0150434. doi: 10.1371/journal.pone.0150434. eCollection 2016. IF: 3.234
For more publications, click on PubMed:
Adresse: Lymphocytes differentiation, tolerance and metabolism: basis for immunotherapy.
Centre: Institute for Regenerative Medicine and Biotherapy.
CHU Montpellier Hôpital Saint-Eloi
80, av. Augustin Fliche.
34295 Montpellier Cedex 5
tel: +33 (0)4 61 33 04 65
fax: +33 (0)4 61 33 01 13
VILLALBA Martin (DR2/CNRS)
GITENAY Delphine (MCU/University of Montpellier)
ALEXIA Catherine (IE/INSERM)
YANG LU Zhao (Biologist/CHRU)
RENE Céline (AIT/UM-CHRU)
ALLENDE-VEGA Nerea (Engineer/CDD-CHRU)
SANCHEZ Diego (Postdoc/INSERM)
KHAN Abrar Ul Haq (Doctorant/UM)
VO Dang-Nghiem (Doctorant/CDD
BELKHALA Sana (Doctorant/UM)
GABELLIER Ludovic (Master student/CHU)
in vitro expansion
hematological cancers immunotherapy
tumor cell metabolism
We specialize in identifying lymphocyte’s populations in normal and pathological conditions (qPCR, flow cytometry, cell sorting). In addition, we are experts in expanding lymphocyte’s populations in vitro (cell culture, GMP conditions, umbilical cord blood). We have described new metabolic pathways that govern immune cell recognition of tumor cells (ex vivo cell metabolism, culture under OXPHOS).